Deep learning-based correction of cataract-induced influence on macular pigment optical density measurement by autofluorescence spectroscopy.

PURPOSE: Measurements of macular pigment optical density (MPOD) using the autofluorescence spectroscopy yield underestimations of actual values in eyes with cataracts. Previously, we proposed a correction method for this error using deep learning (DL); however, the correction performance was validated through internal cross-validation. This cross-sectional study aimed to validate this approach using an external validation dataset. METHODS: MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity were measured using SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 (training dataset inherited from our previous study) and 157 eyes (validating dataset) before and after cataract surgery. A DL model was trained to predict the corrected value from the pre-operative value using the training dataset, and we measured the discrepancy between the corrected value and the actual postoperative value. Subsequently, the prediction performance was validated using a validation dataset. RESULTS: Using the validation dataset, the mean absolute values of errors for MPOD and MPOV corrected using DL ranged from 8.2 to 12.4%, which were lower than values with no correction (P < 0.001, linear mixed model with Tukey's test). The error depended on the autofluorescence image quality used to calculate MPOD. The mean errors in high and moderate quality images ranged from 6.0 to 11.4%, which were lower than those of poor quality images. CONCLUSION: The usefulness of the DL correction method was validated. Deep learning reduced the error for a relatively good autofluorescence image quality. Poor-quality images were not corrected.

Inter-device concordance of Veggie Meter-A reflection spectroscopy to measure skin carotenoids.

The Veggie Meter® (VM) is a refraction spectrometer that detects skin carotenoids. We tested the variability of the two modes (single-scan and averaging modes) of four VMs of three different versions (VM-1, 2, 3, 4) with 92 healthy volunteers. Both the modes exhibited a high intra-class correlation coefficient (ICC); however, the averaging mode had a significantly lower coefficient of variance than the single-scan mode. The Bland-Altman analysis showed a systematic error between VM-1 and other three VMs. The actual errors between the VM-1 and the other three VMs in the averaging mode were 7.4%, 10.4%, and 11.8% of the median of VM scores, but the errors could be reduced to 2.8%, 6.3%, and 7.0% by compensating VM scores using the regression equations. Averaging mode had higher accuracy than single-scan mode. The reliability of the VMs was validated by the small coefficient of variation and high ICC. The error was improved using linear regression compensation.

Lutein and Zeaxanthin Distribution in the Healthy Macula and Its Association with Various Demographic Factors Examined in Pseudophakic Eyes.

The macular pigment consisting of lutein (L) and zeaxanthin (Z) protects photoreceptors via its antioxidative and barrier activities. This study aimed to determine L and Z distribution in the healthy macula and their association with various demographic factors. Macular pigment optical density (MPOD) was measured using fundus autofluorescence spectroscopy in 352 pseudophakic eyes with no fundus diseases. Pseudophakia was chosen to avoid the influence of cataract in the measurement of fundus autofluorescence. The mean patient age was 72.3 ± 8.6 years. MPOD was analyzed separately in three zones, i.e., A: a central area within a radius of 0.5°, mainly containing Z; B: a ring area with radii from 0.5° to 1.3°, containing Z and L; C: a ring area with radii from 1.3° to 9°, containing L. Multivariate analyses were performed with MPOD as the dependent variable and sex, supplement intake, smoking habits, glaucoma, diabetes, age, body mass index (BMI), skin carotenoid levels, retinal thickness, retinal volume, axial length as the independent variables. The mean total MPOD volume within 9° eccentricity was 20,121 ± 6293. Age was positively associated with MPOD in all zones. Supplement and BMI were positively and negatively associated with MPOD in zones B and C. Smoking was negatively associated with MPOD in zone A. This study revealed the standard MP values of aged Japanese, which resulted to be higher than the previously reported values in other races. Age was found to have a positive association with MP values. L in the outer foveola was affected by BMI and supplements, but Z in the foveola was not. The amount of Z in the Müller cell cone may not be changed easily by factors such as hunger and satiety in the context of preservation of homeostasis in the human body, but tobacco had a negative effect on Z.

Correction for the Influence of Cataract on Macular Pigment Measurement by Autofluorescence Technique Using Deep Learning.

Purpose: Measurements of macular pigment optical density (MPOD) by the autofluorescence technique yield underestimations of actual values in eyes with cataract. We applied deep learning (DL) to correct this error. Subjects and Methods: MPOD was measured by SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 eyes before and after cataract surgery. The nominal MPOD values (= preoperative value) were corrected by three methods: the regression equation (RE) method, subjective classification (SC) method (described in our previous study), and DL method. The errors between the corrected and true values (= postoperative value) were calculated for local MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity. Results: The mean error for MPODs at four eccentricities was 32% without any correction, 15% with correction by RE, 16% with correction by SC, and 14% with correction by DL. The mean error for MPOV was 21% without correction and 14%, 10%, and 10%, respectively, with correction by the same methods. The errors with any correction were significantly lower than those without correction (P < 0.001, linear mixed model with Tukey's test). The errors with DL correction were significantly lower than those with RE correction in MPOD at 1° eccentricity and MPOV (P < 0.001) and were equivalent to those with SC correction. Conclusions: The objective method using DL was useful to correct MPOD values measured in aged people. Translational Relevance: MPOD can be obtained with small errors in eyes with cataract using DL.

Macular pigment changes after cataract surgery with yellow-tinted intraocular lens implantation.

PURPOSE: We previously reported that macular pigment optical density (MPOD) levels decreased during a long follow-up period after clear intraocular lens (IOL) implant surgery presumably due to excessive light exposure. We examined changes in MPOD levels in the eyes that received yellow-tinted IOL implant surgery. SUBJECTS AND METHODS: This was a prospective, observational study. Fifty-five eyes of 35 patients were studied. MPOD levels were measured with a dual-wavelength autofluorescence technique on day 4; months 1, 3, and 6; and years 1 and 2 postoperatively. The average optical densities at 0°- 2° eccentricities (local MPODs) and total volumes of MPOD (MPOVs) in the area within 1.5° and 9° eccentricities were analyzed. RESULTS: The mean local MPOD at baseline (on day 4) was 0.79 at 0°, 0.71 at 0.5°, 0.68 at 0.9°, and 0.32 at 2°. The mean MPOV within 1.5° and 9° at baseline was 2950 and 18,897, respectively. Local MPOD at 0.9° and 2° and MPOVs were slightly decreased at month 1 and increased after that. The increase reached statistical significance in local MPOD at 0.5° and 2° and MPOVs (Tukey-Kramer test). The changes in MPOV within 9° at year 2 [(MPOV on year 2 - MPOV on day 4) / MPOV on day 4] were from -0.21 to 1.18 (mean and standard deviation: 1.14 ± 0.28). The MPOV of 15 eyes increased more than 10% from the initial value, was maintained within 10% in 21 eyes, and deteriorated more than 10% in only 3 eyes. CONCLUSIONS: Local MPOD and MPOV tended to slightly decrease month 1 postoperatively and gradually increased after that, but the rates of increases in MPOD levels were small. Yellow-tinted IOLs that have a lower transmittance of blue light might be preferable for preserving MPOD levels after surgery.

Evaluation of Relevance between Advanced Glycation End Products and Diabetic Retinopathy Stages Using Skin Autofluorescence.

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.

Macular Pigment in Eyes With Macular Hole Formation and Its Change After Surgery.

Purpose: To observe the macular pigment (MP) appearances in eyes with macular hole (MH) and clarify the origin of the appearances. The mechanisms underlying the development of MH are discussed based on the observation of MP. Methods: This observational case series included 33 eyes of 31 patients with MH who underwent vitrectomy. The MP optical density was measured using the two-wavelength fundus autofluorescence technique. The exact localization of MP was evaluated by comparing MP distribution images and optical coherent tomography B-scan images. Results: MP was missing at the MH. The area of the MP defect corresponded with the area of the defect of outer plexiform layer. MP was present in the retinal flap in stage 2 MH that included glia (Müller cells) and plexiform layers and in the operculum in stage 3 MH, which mainly comprised Müller cells. Cystic spaces in the outer plexiform layer surrounding stage 3 and 4 MHs showed a honeycomb appearance on MP images. MP reappeared to form an irregularly shaped pigment plane after surgical closure of MH. The MP optical volume did not change before and after surgery. Fellow eyes with a central dip in MP distribution subsequently developed MH. Conclusions: The characteristic appearances of MP at the MH were attributed to MP in the plexiform layers and Müller cell cones. A central dip of MP distribution might be a sign of Müller cell cone damage that proceeds with MH formation. Translational Relevance: Observation of MP was useful for understanding the mechanisms of MH formation.

Advanced Glycation End Product Accumulation in Subjects with Open-Angle Glaucoma with and without Exfoliation.

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs' accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard ß = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (-0.18) and smoking (-0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome.

Potential roles of MNREAD acuity charts and contrast/glare sensitivity in Ranibizumab treatment of branch retinal vein occlusion.

BACKGROUND/OBJECTIVES: To investigate the potential utility of MNREAD acuity charts and contrast/glare sensitivity (CGS) assessment for evaluating the efficacy of an initial treatment with ranibizumab (Lucentis®) for branch retinal vein occlusion (BRVO). METHODS: Intravitreal injections of ranibizumab were administered in 43 eyes of 43 treatment-naïve patients with BRVO. Efficacy was assessed 1 month later. Best-corrected far/near visual acuity (BCFVA/BCNVA), MNREAD parameters (reading acuity [RA], maximum reading speed [MRS], critical print size [CPS]), CGS (CS/GS), and central macular thickness (CMT) in optical coherence tomography (OCT) before and after treatment were evaluated. The area (superior/inferior) affected by BRVO was determined by fluorescein angiography. RESULTS: All parameters improved significantly following treatment (p < 0.05), and all MNREAD and CGS parameters were significantly correlated with BCVA in the treated eye before and after treatment (p < 0.01). The changes in BCFVA, BCNVA, MRS, and CS were significantly correlated with the amount of change in CMT (p < 0.007; r = 0.415, 0.528, -0.465, and -0.508, respectively). MRS exhibited a percentage change that was significantly correlated with that in CMT (p < 0.007; r = -0.511). Additionally, MRS exhibited the lowest threshold CMT (397 µm) at which the most significant change in improvement was observed. CMT was less likely to improve if BRVO occurred at a superior site than if it occurred at an inferior site (0.05 < p = 0.07 < 0.1). CONCLUSIONS: MNREAD and CGS testing were useful for evaluating BRVO treatment efficacy. MRS might be a valuable index for evaluating treatment success and making treatment decisions.

Effect of an antioxidant supplement containing high dose lutein and zeaxanthin on macular pigment and skin carotenoid levels.

The effect of a high dose lutein/zeaxanthin supplement on macular pigment optical density (MPOD) and skin carotenoid (SC) levels in healthy subjects was investigated. This is a prospective, single-arm, open-label study. Subjects were 16 Japanese, age 26-57 years. Subjects took a supplement containing 20 mg/day of lutein, 4 mg/day of zeaxanthin, and other antioxidants (vitamin C, vitamin E, zinc, copper) for 16 weeks. MPOD levels were measured by a two-wavelength autofluorescence imaging technique. SC levels were measured by reflection spectroscopy. Total volume of MPOD within 9° eccentricity significantly increased by week 8 and continued to increase until week 16 (p < 0.0001, two-way factorial ANOVA). The increase rate of MPOD was significantly higher in subjects with body mass index (BMI) less than 25 kg/m2 (n = 13) compared to those of 25 kg/m2 and higher (n = 3). SC levels increased significantly by week 4 and continued to increase until week 16 (p < 0.0001, two-way factorial ANOVA). All subjects completed the study without any serious adverse events. These results demonstrated the effectiveness of a high dose lutein/zeaxanthin supplement for MPOD volume and SC levels without serious adverse events.

Spatial distribution of macular pigment estimated by autofluorescence imaging in elderly Japanese individuals.

PURPOSE: To determine the spatial distribution types of macular pigment (MP) in elderly Japanese individuals and to consider their origin. STUDY DESIGN: Observational case series. METHODS: Local MP optical density (MPOD) at some eccentricities and MP volume were measured using the MPOD module of a MultiColor Spectralis in 96 pseudophakic eyes of 96 participants (age range, 52-86 years; mean age, 72.8 ± 8.3 years). The MP distribution types were determined from the MP spatial profiles. The retinal thickness (RT) at the foveal center, at both 0.5° and 0.9° eccentricities, and the foveal width were measured using optical coherence tomography. RESULTS: The mean local MPOD at the foveal center was 0.79. Spatial distribution was classified into four types: central peak (24.0%), ring-like (40.6%), intermediate (22.9%), and central dip (12.5%). The ring-like type was the most frequent in these Japanese participants. The central-peak type showed lower MPOD than did the other types in the area outside 0.9°. The ring-like type occurred frequently in eyes with small RT at 0.5° and wider foveal width. A rough contour of the Müller cell cone was found more frequently in the central-dip type than in the other types. CONCLUSIONS: The present characteristics of the different distribution patterns could be explained by the hypothesis that MP presents mainly in the Müller cell cone within 0.5° and in Müller cells in the outer and inner plexiform layers in the area outside 0.5°. The anatomic characteristics of Müller cells at the fovea and parafovea likely affect the MP distribution.

Skin Carotenoid Index in a large Japanese population sample.

Carotenoids are anti-oxidative agents. Human skin and eyes contain specific carotenoid species known to prevent various pathologies caused by oxidative stress. We quantified skin and eye carotenoid levels and investigated their potential correlation in a population including 985 Japanese patients and staff members of an ophthalmology clinic (577 men, 408 women, mean age of 69.7 ± 13.6 [SD]). Skin carotenoid (SC) and macular pigment (MP) levels were measured with reflection spectroscopy and autofluorescence imaging methods, respectively. The mean SC index was 343.1 ± 142.1 (SD). SC indices for women were higher than for men (382 vs 315, p < 0.001). Smokers and overweight subjects (BMI ≥ 25) had lower SC indices. Subjects taking lutein supplements had higher SC indices than non-supplementing subjects (415 vs 325, p < 0.001). SC and MP indices were significantly correlated. The obtained data set can be used for reference purposes by Japanese subjects and researchers interested in tissue responses to diets high in carotenoids and lutein supplementation.

Optic coherence tomography appearances of retinal astrocytic hamartoma and systemic features in tuberous sclerosis of Japanese patients.

PURPOSE: To describe the optical coherence tomography findings of retinal astrocytic hamartoma of tuberous sclerosis and to confirm the association between the type of retinal astrocytic hamartoma and systemic manifestations in Japanese patients. STUDY DESIGN: A retrospective observational case series. METHODS: The medical records of 35 patients with tuberous sclerosis who underwent ophthalmological examination were reviewed. The retinal astrocytic hamartomas were classified into four types based on the optical coherence tomography findings, and their association with systemic disease was evaluated. RESULTS: A total of 40 retinal astrocytic hamartomas in 13 eyes of eight patients aged 4-28 years were identified. Optical coherence tomography images were obtained for 23 lesions in 10 eyes of seven patients. Retinal astrocytic hamartomas were seen as protruding lesions of varying heights (maximum thickness, range between 221 to 1043 µm). Of the 23, 15 lesions showed homogeneous reflectivity; in six lesions, hyper-reflective spots that presumably represented intratumoral calcification were noted. Vitreous changes were noted in 13 lesions; vitreous seeding by retinal astrocytic hamartoma was observed in seven eyes. There were no significant differences in the rates of each systemic feature among the optical coherence tomography types. CONCLUSION: Retinal astrocytic hamartomas were classified into four types according to the previous reports; however, this classification may be worthless because the extent of protrusion did not correspond to the intratumoral characteristics, and the involved depth of the retina was not same even in the same type. An association between the type of retinal astrocytic hamartoma and systemic manifestations was not confirmed in this small case series. We considered that the classification of retinal astrocytic hamartoma and its association with systemic manifestations need further study.

Optical Detection of Macular Pigment Formation in Premature Infants.

PURPOSE: To demonstrate the presence of macular pigment in the retina of premature infants, and to examine its changes with age. METHODS: The participants included 40 premature infants. Infants who had received laser photocoagulation for retinopathy of prematurity were excluded. Macular pigment optical density (MPOD) was measured by fundus reflectometry using RetCam3, a digital fundus camera. The reflection imaging was performed for ROP screening. The imaging time points were from a post menstrual age (PMA) of 29 weeks 0 days to 46 weeks 5 days. RESULTS: The MPOD levels could be obtained from 39 premature infants. The levels at the first measurement ranged from 0 to 0.18 (mean 0.076, SD 0.044). The earliest time, when a nonvanishing MPOD level was obtained, was at a PMA of 33 weeks and 2 days, and that level was 0.05. The initial examination MPOD levels showed a moderate correlation with age (R2 = 0.32, P < 0.00017). The mean MPOD levels measured each week during the follow-up period showed a very strong correlation with age (R2 = 0.91, P < 0.0001). A regression line of MPOD = 0.0069 × age - 0.1783 was derived, where age is counted in PMA days. CONCLUSIONS: The MPOD levels of premature infants were for the first time measured in living eyes. Macular pigment increased linearly with age. TRANSLATIONAL RELEVANCE: Macular pigment increased with the development of macular morphology. This result suggested the importance of nutritional management of infants and mothers during perinatal period.

Grade of Cataract and Its Influence on Measurement of Macular Pigment Optical Density Using Autofluorescence Imaging.

Purpose: To evaluate the influence of cataracts on measuring macular pigment optical density (MPOD) using a dual-wavelength confocal scanning autofluorescence imaging technique and to establish methods to compensate for the influence of cataracts. Methods: This prospective case series comprised 100 eyes that underwent cataract surgery. Cataracts were graded based on the World Health Organization classification. MPOD levels were measured with the MPOD module of the Spectralis MultiColor instrument (Spectralis-MP), pre- and postoperatively. We investigated the relationship between change in MPOD values and age, cataract grade, and quality of autofluorescence images. Local MPOD levels were evaluated for four strategically chosen eccentricities within the macular region, and the total MPOD volume was evaluated within 8.98° eccentricity from the center. Results: MPOD levels could be obtained in 67 eyes before surgery. Local and volume MPOD levels were higher postoperatively relative to preoperatively in all eyes. The mean ratio of local MPOD levels after and before surgery (correction factor, CF) ranged from 1.42 to 1.77, with larger CFs required for eccentricities closer to the foveal center. The CF for the MPOD volume was 1.31. Age, grade of nuclear cataract (NUC), posterior subcapsular opacity, and image quality index (IQI) significantly contributed to CFs. For example, regression equation for CF at 0.23° = 0.17 + 0.16 × IQI + 0.29 × NUC grade + 0.01 × age (P < 0.001). Conclusions: Cataracts affected MPOD measurements with the Spectralis-MP, but corrected MPOD results could be obtained via regression equations.

Reliability of a commercially available heterochromatic flicker photometer, the MPS2, for measuring the macular pigment optical density of a Japanese population.

PURPOSE: The macular pigment optical density (MPOD) of a Japanese population was measured using a commercially based heterochromatic flicker photometer, the Macular Pigment Screener (MPS2). The objective of the study was to evaluate the accuracy and test-retest reliability of the MPS2 in Asian pigmented eyes. STUDY DESIGN: Experimental study to validate the medical instrument in humans. METHODS: Twenty-four healthy Japanese participants with no systemic or eye diseases (men: 13, women: 11; mean [SD] age 38.6 [10.9 years]) were included. The concordance of the MPOD, obtained using the MPS2 and Macular Metrics II (MM2), and the test-retest reliability were examined. RESULTS: Determination of the MPOD was unsuccessful in 1 participant; thus, the MPOD of 23 participants was analyzed. The mean (SD) MPOD measured with the detail-mode of the MPS2 was 0.63 (0.18) and with that of the MM2, it was 0.72 (0.23). The former was significantly lower than the latter (P = .003, paired t test). The MPOD measured with the MPS2 and the MM2 showed good concordance (r = 0.79, P < .001, Pearson product moment correlation). Bland-Altman analyses showed no systematic errors between the MPS2 and the MM2. The intraclass correlation coefficient over 5 measurement times with the detail-mode of the MPS2 was 0.80, and the mean coefficient of variation was 9.4%. CONCLUSION: The high concordance with the MM2 and good test-retest reliability found by this study suggest that the MPS2 is acceptable for use in a Japanese population. However, the mean MPOD yielded by the MPS2 was significantly lower than that yielded by the MM2. Therefore, the MPS2 and MM2 are not interchangeable in a single study.

Reliability of a two-wavelength autofluorescence technique by Heidelberg Spectralis to measure macular pigment optical density in Asian subjects.

This study evaluates the accuracy of an objective two-wavelength fundus autofluorescence technique for the purpose of measuring the macular pigment optical density (MPOD) in Asian pigmented eyes. Potential differences between MPOD values obtained via autofluorescence technique and subjective heterochromatic photometry (HFP) were examined. Inter-examiner reproducibility between three examiners and test-retest reliability over five time points were also explored. Subjects were 27 healthy Japanese volunteers aged 24 to 58 (mean ±â€¯standard deviation, 40.2 ±â€¯9.0) years. An MPOD module of the Spectralis MultiColor instrument configuration (Spectralis-MP) was used for the autofluorescence technique, and a Macular Metrics Densitometer (MM) was used for HFP. The mean MPOD values at 0.25° and 0.5° eccentricities using the Spectralis-MP were 0.51 ±â€¯0.12 and 0.48 ±â€¯0.13, respectively. In comparison, the MM based values were 0.72 ±â€¯0.23 and 0.61 ±â€¯0.25, respectively. High correlations between the Spectralis-MP and MM instrument were found (Pearson's correlation coefficients of 0.73 and 0.87 at 0.25° and 0.5° eccentricities, respectively), but there was a systematic bias: the MPOD values by MM method were significantly higher than those by Spectralis-MP at 0.25° eccentricity. High inter-examiner reproducibility and test-retest reliability were found for MM measurements at 0.5° eccentricity, but not at 0.25°. The Spectralis-MP showed less inter-examiner and test-retest variability than the MM instrument at 0.25° and 0.5° eccentricities. We conclude that the Spectralis-MP, given its high agreement with the HFP method and due to its higher reproducibility and reliability, is well suited for clinical measurements of MPOD levels in Asian pigmented eyes.

Evidence of Carotenoid in Surgically Removed Lamellar Hole-Associated Epiretinal Proliferation.

Purpose: To determine the constituents and origin of the yellow pigment in surgically removed lamellar hole-associated epiretinal proliferation (LHEP) in patients with lamellar macular hole (LMH). Methods: This prospective case series comprised nine eyes with LMH in patients aged 41 to 83 years. The presence of LHEP was confirmed by preoperative optical coherence tomography; the distribution of macular pigment was observed by two-wavelength fundus autofluorescence technique before and after surgery. The subjects underwent a 25-gauge vitrectomy, and the surgically removed epiretinal membranous tissue was fixed with formalin. The specimens were examined using resonance Raman microscopy, and paraffin sections were stained with antiglial fibrillary acidic protein. Results: Seven cases presented with LHEP, and the presence of yellow pigment was confirmed using an operating microscope. Carotenoid-specific Raman signals with three major Raman peaks could be identified in the specimens with LHEP. These specimens were positive for glial fibrillary acidic protein staining. Using the fundus autofluorescence technique, a central defect in the distribution of the macular pigment was noted in the exact area of the lamellar hole. This type of defect was no longer visible after surgical repair of the lamellar hole. Conclusions: The constituents of the yellow pigment in the removed LHEP were carotenoids that typically originate from the macular xanthophyll pigments at the fovea. Since LHEP is reported to be composed of Müller cells, we hypothesize that xanthophyll carotenoids at the fovea are contained in the Müller cells.

[Anti-vascular Endothelial Growth Factor Therapy on Exudative Age-related Macular Degeneration in Routine Clinical Practice of a Single Site: the Effectiveness of Cases Followed for More than Two Years].

PURPOSE: To investigate the long-term effectiveness of as-needed anti-vascular endothelial growth factor therapy on age-related macular degeneration (AMD). SUBJECTS AND METHODS: The number of treatments, treatment period, visual acuity and morphological changes were investigated retrospectively in 257 eyes of 248 patients (189 men and 59 women, mean age ± SD; 71.1 ± 9.2 years old) who were followed up for two years and more. Re-treatment was mainly decided based on patient's will. RESULTS: The mean number of treatments was 6.4 3.8 in the observational period of 3.7 years. Exudative changes were resolved at least once in the observational period in 240 eyes, and 160 eyes had no exudative changes at the final visit. Type 2 neovascularization by Gass resulted in fibrotic scar more frequently than type 1. The mean decimal visual acuity was 0.36 before the initiation of treatment and 0.26 at the final visit. The treatment period was less than 100 days in 54 eyes, and multivariate analysis revealed that polypoidal choroidal vasculopathy (PCV) was a factor of prolonged treatment period. No severe adverse effects were admitted locally and systemically. CONCLUSIONS: The deterioration of mean visual acuity was assumed to be due to the relatively small number of treatments. Twenty-one percent of all eyes preserved well without any recurrence of treatments for short periods, and PCV needed treatments for longer periods than typical AMD.

Changes in Macular Pigment Optical Density and Serum Lutein Concentration in Japanese Subjects Taking Two Different Lutein Supplements.

PURPOSE: To investigate macular pigment optical density (MPOD) and serum concentration changes of lutein in Japanese subjects participating in a clinical trial in which two formulations of lutein and zeaxanthin supplements with different physiochemical properties are used. METHODS: Thirty-six healthy volunteers were recruited into this prospective, randomized, parallel-group, double-masked comparative study at a single institute. Two products were used, FloraGLO® (Kemin Japan) and XanMax® (Katra Phytochem). The lutein particle size and zeaxanthin concentrations differed between the formulations. The subjects consumed one of the two supplements for a duration of up to 6 months. MPOD levels were measured by resonance Raman spectrometry at baseline and once a month until the end of the study. Serum lutein concentration was measured at baseline, month 3, and month 6. The subjects were also tested for contrast sensitivity, glare sensitivity, visual acuity, and in addition had a focal electroretinogram measured. RESULTS: The mean serum lutein concentrations increased significantly after the first three months, but the mean MPOD levels in either supplement group did not show any statistically significant increase. A detailed analysis, however, revealed three response patterns in both groups for the increase of MPOD levels and serum lutein concentration, i.e. "retinal responders", who had an increase of both MPOD levels and serum lutein concentrations (n = 13), "retinal non-responders", who had only increased serum concentrations and no change in MPOD levels (n = 20), and "retinal and serum non-responders", who had neither MPOD level nor plasma concentration increases (n = 3). The subjects with low MPOD levels at baseline appeared to show increased MPOD levels at the 6 month time point upon lutein supplementation (r = -0.4090, p = 0.0133). Glare sensitivity improved in retinal responders in both supplement groups, while there were no remarkable changes in contrast sensitivity. CONCLUSIONS: No statistically significant differences could be detected for MPOD levels and serum lutein concentrations between the two investigated lutein supplement formulations. Responses to lutein supplementation regarding MPOD levels and serum lutein concentrations varied between subjects. Subjects with lower MPOD levels at baseline responded well to lutein supplementation. However, since the number of subjects was low, a further study with more subjects is needed to prove that subjects with low MPOD levels will benefit from lutein supplementation. TRIAL REGISTRATION: UMIN-CTR UMIN000004593.